Selective destruction of nitric oxide synthase neurons with quisqualate reduces damage after hypoxia-ischemia in the neonatal rat

Donna M. Ferriero, R. Ann Sheldon, Stephen Matthew Black, Jing Chuai

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The vulnerability of the developing CNS to hypoxia-ischemia (H-I) differs from that of the mature brain and is due in part to release of nitric oxide (NO) from parenchymal neurons. If NO is important in the generation of excitotoxic injury after H-I in the developing CNS, then selective destruction of the neuronal nitric oxide synthase (nNOS) cells before H-I should lessen the injury seen after the insult. Using low dose quisqualic acid (QA) injected into neonatal (postnatal d 7) parietal cortex, the nNOS neurons were eliminated while sparing other neuronal and glial populations as ascertained by NADPH diaphorase histochemistry, nNOS immunocytochemistry, and Nissl counterstain. Animals subjected to focal ischemia followed by global hypoxia 24 h after the intracortical injection of QA had more viable cortex remaining than vehicle-injected animals (83.4 ± 4.3% versus 62.7 ± 8.3%) and lower injury severity represented by less neuronal loss and gliosis. Intracortical injections of QA without H-I resulted in minimal cell loss at the injection site with elimination of nNOS neurons throughout the parietal cortex. Microglial and astrocytic proliferation was seen in areas damaged by H-I 3 wk after injury and clearly marked infarcted areas. Prevention or elimination of NO production from nNOS cells can prevent much of the delayed neuronal necrosis seen after H-I in the developing CNS.

Original languageEnglish (US)
Pages (from-to)912-918
Number of pages7
JournalPediatric Research
Volume38
Issue number6
DOIs
StatePublished - Jan 1 1995

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Quisqualic Acid
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Ischemia
Neurons
Nitric Oxide
Parietal Lobe
Wounds and Injuries
Injections
NADPH Dehydrogenase
Cell Hypoxia
Gliosis
Hypoxia
Neuroglia
Necrosis
Immunohistochemistry
Brain

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Selective destruction of nitric oxide synthase neurons with quisqualate reduces damage after hypoxia-ischemia in the neonatal rat. / Ferriero, Donna M.; Sheldon, R. Ann; Black, Stephen Matthew; Chuai, Jing.

In: Pediatric Research, Vol. 38, No. 6, 01.01.1995, p. 912-918.

Research output: Contribution to journalArticle

Ferriero, Donna M. ; Sheldon, R. Ann ; Black, Stephen Matthew ; Chuai, Jing. / Selective destruction of nitric oxide synthase neurons with quisqualate reduces damage after hypoxia-ischemia in the neonatal rat. In: Pediatric Research. 1995 ; Vol. 38, No. 6. pp. 912-918.
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